Novel voriconazole-loaded solid lipid nanoparticles (VRC-SLNs) were prepared via probe-ultrasonication method, and the resultant nanoparticles were tested on A. fumigatus. Voriconazole-loaded solid lipid nanoparticles were prepared using the probe ultrasonication technique. Photon correlation spectroscopy (PCS) was used to determine the average particle size and zeta potential of SLN formulations. Transmission electron microscopy was also used to determine the morphology of solid lipid nanoparticles. To determine MIC for all SLN formulations against strains of Aspergillus the Clinical and Laboratory Standards Institute guidelines was followed. The results showed that SLNs containing voriconazole exhibited almost spherical shape with a diameter and zeta potential of 286.6 ± 4.7 nm and −15 ± 4.1 mV respectively. This novel formulation of VRC led to a significant reduction in MICs for all Aspergillus either VRC-susceptible or VRC-resistant isolates (P < 0.05). The MIC50 drug concentration was obtained as 0.015 μg/ml for both VRC-susceptible strains of A. fumigates while it was 0.25 μg/ml against VRC (p < 0.05). VRC-resistant strains showed a MIC50 of 0.015 μg/ml as well. These novel drug formulations may increase the bioavailability through an increase in the dissolution rate of voriconazole. This study showed, for the first time, VRC-SLNs can be employed as an effective delivery systems for VRC on A. fumigatus isolates